U.S. patent number 10,434,329 [Application Number 15/306,495] was granted by the patent office on 2019-10-08 for autofocus wireless power transfer to implantable devices in freely moving animals.
This patent grant is currently assigned to THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY. The grantee listed for this patent is THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY. Invention is credited to Karl Deisseroth, Scott Lee Delp, Emily A. Ferenczi, Logan Grosenick, John S. Y. Ho, Shrivats Mohan Iyer, Kate L. Montgomery, Ada Shuk Yan Poon, Yuji Tanabe, Vivien Tsao, Alexander J. Yeh.
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United States Patent |
10,434,329 |
Poon , et al. |
October 8, 2019 |
Autofocus wireless power transfer to implantable devices in freely
moving animals
Abstract
A power transmitter is provided that can include a microwave
cavity resonant at a desired operating frequency, a hexagonal mesh
top to leak evanescent fields out of the cavity, and a plurality of
orthogonal monopole feeds with 90 degrees phase differences
creating circularly polarized waves. The power transmitter can be
configured to transmit energy to a wireless device implanted in an
animal passing through the evanescent fields. Implantable devices
are also described which can receive wireless energy from the power
transmitter and stimulate the animals (e.g., optogenetic or
electrical stimulation).
Inventors: |
Poon; Ada Shuk Yan (Redwood
City, CA), Ho; John S. Y. (Stanford, CA), Tanabe;
Yuji (Stanford, CA), Yeh; Alexander J. (Palo Alto,
CA), Montgomery; Kate L. (Palo Alto, CA), Grosenick;
Logan (Palo Alto, CA), Ferenczi; Emily A. (Palo Alto,
CA), Tsao; Vivien (Stanford, CA), Iyer; Shrivats
Mohan (Palo Alto, CA), Delp; Scott Lee (Stanford,
CA), Deisseroth; Karl (Palo Alto, CA) |
Applicant: |
Name |
City |
State |
Country |
Type |
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR
UNIVERSITY |
Stanford |
CA |
US |
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Assignee: |
THE BOARD OF TRUSTEES OF THE LELAND
STANFORD JUNIOR UNIVERSITY (Stanford, CA)
|
Family
ID: |
54392831 |
Appl.
No.: |
15/306,495 |
Filed: |
March 25, 2015 |
PCT
Filed: |
March 25, 2015 |
PCT No.: |
PCT/US2015/022509 |
371(c)(1),(2),(4) Date: |
October 25, 2016 |
PCT
Pub. No.: |
WO2015/171213 |
PCT
Pub. Date: |
November 12, 2015 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20170065828 A1 |
Mar 9, 2017 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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61991266 |
May 9, 2014 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N
5/0601 (20130101); A61N 1/3787 (20130101); A61N
5/0622 (20130101); A61N 1/3605 (20130101); A61N
1/0529 (20130101); A61B 5/0031 (20130101); A61B
2560/0219 (20130101); A61N 1/37205 (20130101); A61B
2503/40 (20130101) |
Current International
Class: |
A61N
5/06 (20060101); A61N 1/36 (20060101); A61B
5/00 (20060101); A61N 1/378 (20060101); A61N
1/05 (20060101); A61N 1/372 (20060101) |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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WO2009/008932 |
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Jan 2009 |
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WO |
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WO2011/150430 |
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Dec 2011 |
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WO |
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WO2013/035092 |
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Mar 2013 |
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WO |
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WO2014/006510 |
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Jan 2014 |
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WO |
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WO2014/153219 |
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Sep 2014 |
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WO |
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WO2014/153228 |
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Sep 2014 |
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WO |
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WO2015/039108 |
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Mar 2015 |
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WO |
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WO2015/196164 |
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Dec 2015 |
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WO |
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WO2016/127130 |
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Aug 2016 |
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WO |
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Other References
Zhao et al., RF evanescent-mode cavity resonator for passive
wireless sensor applications, Sensors and Actuators A 161 (2010)
322-328. cited by examiner .
Poher et al., Micro-LED arrays: a tool for two-dimensional neuron
stimulation, J. Phys. D: Appl. Phys. 41 (2008). cited by examiner
.
Liou et al., Wireless Charging System of Mobile Handset Using
Metamaterial Based Cavity Resonator, IEEE, 2012. cited by examiner
.
Wentz et al., A Wirelessly Powered and Controlled Device for
Optical Neural Control of Freely-Behaving Animals, J Neural Eng.
Aug. 2011 ; 8(4). cited by examiner .
Ball; Wireless power for tiny medical devices; Physics; 6; 57; 3
pages; May 17, 2013. cited by applicant .
Ho et al.; Midfield wireless powering for implantable systems;
Proc. IEEE; vol. 101; No. 6; Apr. 4, 2013; 10 pages; retrieved Apr.
21, 2014 from the internet:
http://web.stanford.edu/group/poongroup/cgi-bin/wordpress/wp-co-
ntent/uploads/2013/05/PIEEE%202013%20Ho.pdf. cited by applicant
.
Kim et al.; Midfield wireless powering of subwavelength autonomous
devices; Phys. Rev. Lett.; 110(20); 203905; May 17, 2013. cited by
applicant .
Kim et al.; Wireless power transfer to a cardiac implant; Appl.
Phys. Lett.; 101; 073701; 2012; 5 pages; Aug. 13, 2012. cited by
applicant .
Kim et al.; Wireless power transfer to miniature implants:
transmitter optimization; IEEE Trans. Antennas and Propagation;
vol. 60; No. 10; pp. 4838-4845; Oct. 2012. cited by applicant .
Park et al.; Enhancement of wireless power transmission into
biological tissues using a high surface impedance ground plane;
Progress in Electromagnetics Research; 135; pp. 123-136; 2013;
retrieved Apr. 29, 2015 from the internet:
http://onlinewww.jpier.org/PIER/pier135/08.12110902.pdf. cited by
applicant .
Thomas et al.; Modulated backscatter for ultra-low power uplinks
from wearable and implantable devices; In Proceedings of the 2012
ACM workshop on Medical communication systems; 6 pages; retrieved
from the internet
(http://conferences.sigcomm.org/sigcomm/2012/paper/medcomm/p1.pdf);
Aug. 13, 2012. cited by applicant .
Xu et al.; A novel mat-based system for position-varying wireless
power transfer to biomedical implants; IEEE Transactions on
Magnetics; 49(8); pp. 4774-4779; Aug. 2013. cited by applicant
.
Yeh et al.; Wirelessly powering miniature implants for optogenetic
stimulation; Appl. Phy. Lett.; 103; 163701; 4 pages; Oct. 8, 2013.
cited by applicant.
|
Primary Examiner: Layno; Carl H
Assistant Examiner: Pahakis; Manolis
Attorney, Agent or Firm: Shay Glenn LLP
Government Interests
STATEMENT OF GOVERNMENT SUPPORT
This invention was made with Government support under Contract
NS080954 awarded by the National Institutes of Health. The
Government has certain rights in the invention.
Parent Case Text
CROSS REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of U.S. Provisional Appln. No.
61/991,266, titled "Autofocus Wireless Power Transfer to
Implantable Devices in Freely Moving Animals", filed on May 9,
2014, which is incorporated herein by reference in its entirety.
Claims
What is claimed is:
1. A light delivery system, comprising: a resonant cavity chamber
configured to generate electromagnetic energy, the resonant cavity
chamber comprising a surface lattice of subwavelength apertures
upon which an animal can be placed; and a wirelessly powered
implantable device adapted to be implanted in the animal, the
implantable device comprising: a circuit board; a power receiving
coil coupled to the circuit board and adapted to receive
electromagnetic energy from the resonant cavity; a rectifier
coupled to the circuit board and the power receiving coil and
adapted to convert the electromagnetic energy received in the power
receiving coil into a DC current; a micro-LED coupled to the
circuit board and adapted to provide optogenetic stimulation to the
animal.
2. The light delivery system of claim 1, wherein the implantable
device is configured to be implanted on or adjacent to the animal's
brain.
3. The light delivery system of claim 1, wherein the implantable
device is configured to be implanted on or adjacent to the animal's
spinal cord.
4. The light delivery system of claim 1, wherein the implantable
device is configured to be implanted on or adjacent to nerve
endings of one or more of the animal's limbs.
5. The light delivery system of claim 1, further comprising a
conductive extension coupling the micro-LED to the circuit
board.
6. The light delivery system of claim 1, wherein the implantable
device has a volume ranging between 10 to 25 mm.sup.3.
7. The light delivery system of claim 1, wherein the implantable
device has a mass ranging from 20 to 50 mg.
8. The system of claim 1 further comprising a plurality of monopole
feeds disposed in the resonant cavity chamber.
9. The system of claim 8, wherein the a plurality of orthogonal
monopole feeds are arranged with 90 degrees phase differences so as
to create circularly polarized waves.
Description
INCORPORATION BY REFERENCE
All publications and patent applications mentioned in this
specification are herein incorporated by reference to the same
extent as if each individual publication or patent application was
specifically and individually indicated to be incorporated by
reference.
FIELD
This disclosure is generally related to fully implantable,
wirelessly powered stimulators.
BACKGROUND
Practical and effective light delivery during behavioral modulation
is a key challenge in applying optogenetics to understand and
control neural function. Initial solutions to this problem have
relied on tethered optical fiber-based systems, in which a fiber
optic is inserted into the brain of an animal. Such systems exploit
the stable nature of the brain-skull interface, enabling persistent
optogenetic modulation of identified neural populations. These
systems have been refined over the past decade, such as by allowing
fiber rotation during animal movements using optical and electrical
commutators and by improving the ease of attachment and detachment.
These tethered systems nonetheless impose significant constraints
on experimental design and interpretation, both by requiring
investigators to handle and physically restrain animals to attach
an optical fiber prior to behavioral testing, and by limiting the
environments in which optogenetic experiments can be performed.
Recent efforts have been made to eliminate tethers by delivering
light via wireless headmounted systems. In one design, a
battery-powered, wirelessly-controlled device that delivers light
through a thinned mouse skull with an LED. That system has
subsequently been improved by decreasing its size, and was used to
demonstrate motor activation using optogenetic stimulation of
primary motor cortex. Another solution advanced wireless
optogenetics through the use of a wirelessly powered system that
removed the need for bulky batteries. Another approach developed a
flexible, injectable LED-based system for optogenetic stimulation
that was capable of stimulating deeper brain regions and could be
powered by a head-mountable wireless power receiver.
These advances of wireless optogenetic technology, although
trailblazing, have been limited by the mass and size of the
devices. The reported wireless systems weigh 0.7 to 3 g (the mass
of a mouse head is approximately 2 g). While the smallest
wirelessly powered device weighs 0.7 g, it lacks remote-control.
All previous devices are so large that they protrude several
millimeters beyond the skin and cannot be left attached to the
animal for prolonged periods of time. Head-mountable devices of
this mass and size ultimately limit which central nervous
structures can be targeted, and prohibit optogenetic control of the
spinal cord or peripheral nervous system. Further, they hinder the
animal's freedom of movement and behavior by preventing animals
from entering small enclosures or engaging in normal social
interactions with other mice.
No fully internal device has yet enabled optogenetic control of
neural circuits.
SUMMARY OF THE DISCLOSURE
A light delivery system is provided, comprising a resonant cavity
configured to generate electromagnetic energy and having a surface
upon which an animal can be placed, and a wirelessly powered
implantable device adapted to be implanted in the animal, the
implantable device comprising a circuit board, a power receiving
coil coupled to the circuit board and adapted to receive
electromagnetic energy from the resonant cavity, a rectifier
coupled to the circuit board and the power receiving coil and
adapted to convert RF energy generated in the power receiving coil
into a DC current, a micro-LED coupled to the circuit board and
adapted to provide optogenetic stimulation to the animal.
In some embodiments, the implantable device is configured to be
implanted on or near the animal's brain. In another embodiment, the
implantable device is configured to be implanted on or near the
animal's spinal cord. In an additional embodiment, the implantable
device is configured to be implanted on or near nerve endings of
one or more of the animal's limbs.
In one embodiment, the implantable device further comprises a
conductive extension coupling the micro-LED to the circuit
board.
In one embodiment, the implantable device is as small as 10 to 25
mm.sup.3 in volume.
In another embodiment, the implantable device has a mass ranging
from 20 to 50 mg.
A wirelessly powered implantable device adapted to be implanted in
an animal is also provided, the implantable device comprising a
circuit board, a power receiving coil coupled to the circuit board
and adapted to receive electromagnetic energy from a resonant
cavity, a rectifier coupled to the circuit board and the power
receiving coil and adapted to convert RF energy generated in the
power receiving coil into a DC current, and a micro-LED coupled to
the circuit board and adapted to provide optogenetic stimulation to
the animal.
In some embodiments, the implantable device is configured to be
implanted on or near the animal's brain. In another embodiment, the
implantable device is configured to be implanted on or near the
animal's spinal cord. In an additional embodiment, the implantable
device is configured to be implanted on or near nerve endings of
one or more of the animal's limbs.
In one embodiment, the implantable device further comprises a
conductive extension coupling the micro-LED to the circuit
board.
In one embodiment, the implantable device is as small as 10 to 25
mm.sup.3 in volume.
In another embodiment, the implantable device has a mass ranging
from 20 to 50 mg.
In one embodiment, one or more outer turns of the power receiving
coil can be bent at an angle with respect to one or more internal
turns of the power receiving coil to compensate for rotation of the
implantable device.
A power transmitter configured to transmit wireless energy to a
power receiver is provided, comprising a resonant cavity, a flat
surface positioned above the resonant cavity and comprising a
surface lattice of subwavelength apertures, a plurality of monopole
feeds disposed in the resonant cavity, and a signal generator
configured to provide power to the plurality of monopole feeds to
generate an evanescent field at the surface lattice that transmits
wireless energy to the power receiver when the power receiver is
brought into proximity with the surface lattice.
A method for stimulating an animal is provided, comprising the
method steps of generating evanescent fields with a power
transmitter, transmitting wireless energy from the power
transmitter to a wireless device that is implanted in an animal
passing through the evanescent fields, and stimulating the animal
with the wireless device.
In some embodiments, the generating step comprises generating
evanescent fields with one or more monopole feeds disposed in a
resonant cavity of the power transmitter.
In one embodiment, the method further comprises allowing the animal
to move on or around the power transmitter.
In another embodiment, the method further comprises enclosing the
animal into or near the power transmitter.
BRIEF DESCRIPTION OF THE DRAWINGS
The novel features of the invention are set forth with
particularity in the claims that follow. A better understanding of
the features and advantages of the present invention will be
obtained by reference to the following detailed description that
sets forth illustrative embodiments, in which the principles of the
invention are utilized, and the accompanying drawings of which:
FIG. 1 illustrates one embodiment of a light delivery system
configured to provide light delivery to an animal such as a mouse
using wirelessly powered and fully internal implantable
devices.
FIGS. 2a-2c illustrate various embodiments of fully internal,
wirelessly powered implantable devices configured to emit light in
the brain, spinal cord, and at peripheral nerve endings of a
subject.
FIGS. 3a-3l illustrate step-by-step construction of the implantable
devices of this disclosure.
FIG. 4a is a diagram showing how light power density and efficiency
of the LED are each a function of the power supplied to the
micro-LED.
FIG. 4b shows the fidelity of light output for step-function pulses
of various pulse widths.
FIG. 4c illustrates a calculated light power density across the
width of the behavioral area above resonant cavity.
FIG. 4d-e illustrate the heating of tissue directly adjacent to the
implanted micro-LED.
FIGS. 5a-b show wireless implantable device of FIG. 2a implanted
into of the brain of a rodent and configured for wireless
optogenetic stimulation of the premotor cortex.
FIG. 5c shows how motor stimulation of the left motor cortex can
cause circling behavior with increase in average speed.
FIGS. 5d-f show representative traces of mouse movement during
on-off cycles.
FIG. 6a shows the device of FIG. 2b implanted on the right side of
the dorsal surface of a vertebra in a mouse.
FIG. 6b is a chart showing stimulation of the spinal cord.
FIG. 7a shows the device of FIG. 2c implanted subcutaneously
adjacent to the triceps surae muscles of a mouse with the micro-LED
of the device routed to the heel.
FIG. 7b shows quantification of c-Fos expression that confirms
unilateral activation of ChR2 after optogenetic stimulation.
FIG. 7c illustrates the movement of mice allowed to explore a
two-chamber place aversion setup in which one floor was resting
directly above the resonant cavity.
FIGS. 7d-f are charts showing that the ChR2-expressing mice spent
significantly less time in the resonant cavity chamber than the
non-resonant cavity chamber compared to control YFP-expressing
mice.
FIG. 8 shows one embodiment of a power transmitter comprising a
resonant cavity and a surface lattice of subwavelength
structures.
DETAILED DESCRIPTION
This disclosure describes a novel approach for investigating
neuronal signaling. The approach described herein exploits high
dielectric permittivity of biological tissue to tunnel energy to
the implantable devices in animals, that is, it uses tissue to
facilitate the coupling of energy from the transmitter to the
implanted receiver. Wherever the animal is located, energy can be
tunneled automatically to the implanted receiver.
To enable more sophisticated optogenetic manipulation of neural
circuits throughout the nervous system with limited disruption of
animal behavior, advances in light delivery beyond fiber optic
tethering and large, head-mounted wireless receivers are required.
This disclosure provides embodiments of easy-to-construct,
implantable wireless optogenetic devices. In some embodiments, the
implantable wireless devices can be as small as 20 mg, 10 mm.sup.3,
which is two orders of magnitude smaller than previously reported
wireless optogenetic systems, allowing the entire device to be
implanted subcutaneously. The implantable wireless devices of this
disclosure can be powered with a radio-frequency (RF) power source
and controller, and can be configured to produce sufficient light
power for optogenetic stimulation with minimal tissue heating
(e.g., less than 1 deg C.). While the specific embodiments
described herein discuss optogenetic stimulation, in other
embodiments the implantable devices can be configured to provide
electrical stimulation. Also described herein are three specific
adaptations of an implantable wireless device which allow for
untethered optogenetic control throughout the nervous system
(brain, spinal cord, and peripheral nerve endings) of living
organisms such as mice. While description of the implantable
wireless devices herein are made with respect to mice, it should be
understood that the devices can be implanted in any living
organisms, including humans.
This disclosure provides an easy-to-construct, fully internal
device for wireless optogenetic stimulation of brain, spinal cord,
or peripheral nerve endings that is two orders of magnitude smaller
and lighter than any previously reported wireless optogenetic
systems. The entire stimulator, including a power receiving coil,
circuit, and light emitting diode (LED), can be as small as 10 to
25 mm.sup.3 in volume, with a mass ranging from 20 to 50 mg
depending on the target neural structure, and can be fully
implanted beneath the skin of the animal or human. The small size
of the stimulator allows for implantation in peripheral locations,
such as limbs or the spinal cord, expanding the diversity of
potential stimulation targets beyond the brain. When implanted in
animals, such miniaturized wireless devices allow the animals to
move more freely, within their own home-cage, through obstacles,
into enclosures, and among other animals, and do not require the
animal to be handled just prior to experiments. The implanted
devices described herein can be built with readily available
components and tools, and powered by a custom resonant cavity,
which can be machined commercially, enabling adoption by the
scientific community.
This disclosure also provides embodiments of a power transmitter
that can include a microwave cavity resonant at a desired operating
frequency, a hexagonal mesh top to leak the evanescent fields out
of the cavity, and a plurality of orthogonal monopole feeds with 90
degrees phase differences creating circularly polarized waves. The
power transmitter can be configured to transmit energy to a
wireless device implanted in an animal supported by the hexagonal
mesh top and passing through the evanescent fields. If there is no
animal passing the mesh, the power transmitter merely emits
evanescent fields so the energy leaked out to the air will be
minimal. If there is an animal passing one or multiple cells of the
mesh, due to the high dielectric property of biological tissue
relative to air, energy will be extracted from the cavity through
the evanescent fields to an implanted receiver in the animal.
FIG. 1 illustrates one embodiment of a light delivery system 100
configured to provide light delivery to an animal such as a mouse
using wirelessly powered and fully internal implantable devices.
The light delivery system 100 can comprise a wirelessly powered
implantable device 102 implanted in an animal, such as a mouse. The
device 102 can be powered and controlled using a resonant cavity
104 with a surface lattice 106 of hexagons and a plurality of
monopole feeds (not shown) to couple electromagnetic energy to the
tissue of an animal. A signal generator 108 can provide power to
the monopole feeds of the resonant cavity 104. In one embodiment,
the system can further include one or more phase shifters and/or
power dividers between the signal generator and the resonant
cavity. In some embodiments, the resonant cavity can comprise
aluminum and can be approximately 21 cm in diameter and 15 cm in
height. The surface lattice of hexagons can have a diameter of
approximately 2.5 cm to couple electromagnetic energy at
approximately 1.5 GHz to the tissue of the animal. The animal can
be enclosed into or near the resonant cavity 104 with an enclosure
110, such as a glass cover.
When an animal such as a mouse is placed on the lattice, strong
field confinement occurs within the mouse due to a volume resonance
determined by the dielectric properties and physical dimensions of
the animal. Conventional inductive systems transfer energy through
direct coupling between one coil and another. In this system,
however, the resonant interaction between the cavity and the animal
mediates power transfer to the implanted device. Because energy is
concentrated in the animal at all positions on the lattice, the
power transfer is self-tracking and efficient enough to power the
wireless implant. Unlike radiative alternatives to the resonant
cavity, such as highly directional antennas, here tracking
algorithms are not required to maintain performance within the
cavity.
FIGS. 2a-2c illustrate various embodiments of fully internal,
wirelessly powered implantable devices configured to emit light in
the brain, spinal cord, and at peripheral nerve endings of a
subject. Three versions of the implantable device are described and
illustrated which target three different neural structures,
specifically the premotor cortex of the brain (FIG. 2a), the dorsal
horn of the spinal cord (FIG. 2b), and peripheral nerve endings of
the heel of a limb (FIG. 2c). Each implantable device 102 can
include a power receiving coil 112 disposed in an acrylic potting
material 114, coupled to a rectifier 116 and a circuit board 118.
The implantable devices can be configured to deliver light to the
subject with a micro-LED 120. In the embodiments of FIGS. 2a and
2c, the micro-LED 120 can be coupled to the circuit board 118 with
an extension 122, which can comprise a pair of magnetic wires. In
one specific embodiment, the extension 122 can comprise a pair of
250 .mu.m diameter magnetic wires. In the embodiment of FIG. 2b,
the micro-LED 120 can be coupled directly to the circuit board to
avoid penetrating the spinal cord.
Each implantable device of FIGS. 2a-2c can be implanted entirely
under the skin of the animal, with a negligible change to the
animal's profile. The circuit board and power receiving coil can be
configured to deliver current to the micro-LED. In some
embodiments, the micro-LED can be a blue LED designed to activate
channelrhodopsin (ChR2). Acrylic encapsulation of the implant
resists biological degradation and electrically insulates the
circuitry. Due to the concentration of electromagnetic energy from
the resonant cavity, and the low gigahertz frequencies used, power
receiving coils can be used to harvest power in the implantable
devices that are significantly smaller (e.g., 1.6 mm diameter) than
conventional inductive systems.
FIGS. 3a-3l illustrate step-by-step construction of the implantable
devices of this disclosure. To give a reference for scale, the
black scale bars in the figures measure 1 mm, and the white scale
bars in the figures measure 0.5 mm. FIG. 3a shows the printed
circuit board (PCB) cut to size, and solder paste applied to the
metal traces on the PCB. FIG. 3b shows the surface-mount devices
(SMD) bonded with reflow soldering. FIG. 3c illustrates the power
receiving coil soldered to the PCB. In one embodiment, the power
receiving coil can be constructed by wrapping wire around
appropriately sized tubing and cutting the wires with wire cutters.
The coil for the brain and spinal cord implants can comprise of 3
turns of 34 gauge magnet wire with an inner diameter of
approximately 1.6 mm. The coil for the peripheral implant can have
an approximate 1.8 mm diameter and the outer turns of the coil can
be bent 45 degrees with respect to the internal turns of the coil
to compensate for the rotation of the implant along the axis of the
coil. In FIG. 3d, the coil and SMD components were stabilized with
acrylic. FIG. 3e shows the extension formed from a pair of twisted
36 AWG wires. In FIG. 3f, ends of the twisted wires were separated
by 70 .mu.m. FIG. 3g illustrates solder paste applied to the tips
of the bared wires. In FIG. 3h, the micro-LED is shown placed on
the ends of the wires. In one embodiment of the brain implant, the
micro-LED can be mounted downwards to deliver light to target
regions within the brain. Thus, the exposed copper at the end of
the two wires can form two conductive pads for the terminals of the
micro-LED. For the peripheral implant, the micro-LED can be mounted
to the side of the extension to deliver light through the skin. In
this specific embodiment, the coating on a 1-mm section on the
sides of the wires near the tip is removed to form two conductive
pads. The twisted magnet wires can then be clamped vertically to a
soldering wire holder. In FIG. 3i, the extension is shown
positioned for reflow with a butane torch, and in FIG. 3j the
extension is cut to the desired length and tested for polarity. In
FIG. 3k, the extension is illustrated soldered to the bottom of the
PCB. Finally, in FIG. 3l, the extension is shown bent to the
desired angle and a final coat of acrylic was applied.
The implantable device of FIG. 2a can be rigidly cemented to the
skull or the subject animal, with the short extension and downward
facing micro-LED penetrating the surface of the brain, similar to
traditional optical fiber implants. An extension is not included in
the implantable device of FIG. 2b to minimize damage to the spinal
cord. Instead, the micro-LED in that embodiment is mounted directly
on the circuit board to avoid penetrating the cord. The peripheral
implant of FIG. 2c can be configured to deliver light
subcutaneously using a long, flexible extension (i.e., longer than
the extension of the FIG. 2a embodiment). Peripheral implants
change spatial orientation relative to the cavity more than central
ones during the natural course of locomotion. Due to this
variability in orientation of the peripheral implant, the
individual turns of the power receiving coil can be set to be
non-parallel, thus minimizing orientation-related power
fluctuations.
The wirelessly powered implantable devices described herein can
generally comprise two main parts. The first part of the device is
the power receiver including the power receiving coil and the
rectifier. The power receiving coil is configured to extract RF
energy coupled from the resonant cavity to the target animal. The
rectifier is configured to convert the RF energy into DC current.
In one embodiment, the rectifier can be implemented by a two-stage
voltage doubling circuit using Schottky diodes. All rectifier and
power receiving coil components can be bonded to a circuit board
made of Roger PCB material for its flexibility for ease of cutting.
The second part of the device is the light delivery portion,
routing the DC current from the rectifier to a micro-LED designed
to be implanted directly at the stimulation site.
As described above, for the spinal cord implant (FIG. 2b), the LED
can be directly attached to the bottom of the PCB. For the brain
and peripheral implants (FIGS. 2a and 2c, respectively), a pair of
magnet wires can be used to route the DC current from the rectifier
to the micro-LED, which can be attached at the tip of the wires. In
some embodiments, the diameter of this extension is about 250
.mu.m.
The implantable devices described herein provide light power
densities and pulse characteristics suited for optogenetic
stimulation without generating excessive heat. FIG. 4a is a diagram
showing how light power density and efficiency of the LED are each
a function of the power supplied to the micro-LED. Here, power is
supplied in the wireless implant by captured and rectified energy.
Light power density can be adjusted by varying the input power to
the resonant cavity. To characterize this, the emitted light power
from the micro-LED can be measured when supplying the micro-LED
with a known current via wired circuitry. The light power density
can then be estimated as a function of input power to the
micro-LED, shown in FIG. 4a. Over the range of light power
densities suitable for optogenetic stimulation (1 to 20 mW/mm2),
the micro-LED of the present disclosure is efficient (emitted light
power/input power=19%).
FIG. 4b shows the fidelity of light output for step-function pulses
of various pulse widths. The relative transient intensities (a.u.)
for 100 .mu.s, 5 ms, 10 ms, and 5 s pulses are shown. In some
embodiments, pulses as short as 100 .mu.s can be delivered without
decay in peak relative power. Towards the bottom of FIG. 4b,
consecutive 5 ms pulses are shown, indicating no loss of light
output fidelity with consecutive pulses.
FIG. 4c illustrates a calculated light power density across the
width of the behavioral area above resonant cavity. The left side
of FIG. 4c shows the resonant cavity with positions 1-7 spanning
across the cavity, and the right side of FIG. 4c shows the light
power density at positions 1-7 of the cavity.
FIG. 4d illustrates the heating of tissue directly adjacent to the
implanted micro-LED. More specifically, FIG. 4d shows the change in
local tissue temperature resulting from a wired micro-LED being
inserted into brain, operating with a light power density of 40
mW/mm2 at 5%, 10%, and 20% duty cycles (5 ms pulse width; 10 Hz, 20
Hz, and 40 Hz frequencies, respectively). FIG. 4e shows that the
temperature change resulting from optogenetic stimulation with
micro-LEDs of the present disclosure stabilizes below levels
typically associated with neural damage (1 degree C.).
Efficient micro-LEDs lead to minimal temperature increases in vivo.
The local temperature of tissues can increase at sites of light
stimulation due to the absorption of photons by tissue and heat
dissipation of the micro-LED. This is concerning, as such heating
could result in tissue damage or artifactual changes in neural
activity (i.e., not optogenetically driven). The implantable
devices of the present disclosure are configured to avoid this
concern by using highly efficient micro-LEDs that produce
sufficient light power for optogenetic stimulation but result in
minimal heating of the surrounding tissue. The optogenetic
stimulation can result in a small but consistent general whole body
heating in the subject, on the order of 0.5 degrees C. greater than
control, of the animal due to absorption of RF energy from the
concentrated electromagnetic field created by the power source and
resonant cavity. For example, normal mouse body temperature varies
between 34 degrees C. and 39 degrees C., and during testing the
electromagnetic field did not cause fluctuations outside of this
temperature range.
FIGS. 5a-b show wireless implantable device of FIG. 2a implanted
into of the brain of a rodent and configured for wireless
optogenetic stimulation of the premotor cortex (M2). As shown in
FIG. 5a, the device can be implanted such that the circuit board
and coil are above the skull and below the skin of the animal, and
the micro-LED at the tip of the extension is inserted into the
brain directly above motor cortex. FIG. 5b illustrates how
implantation can be performed using a stereotactic frame with
implantation tool bonded to the device. The extension and micro-LED
of the device can be inserted into the brain of the mouse, and the
coil and board can be bonded to the skull. The implantation tool
can then be removed from device, and the skin of the animal can be
sutured over the device. In one embodiment, the total implantation
time can be approximately 30 minutes.
FIG. 5c shows how motor stimulation of the left motor cortex can
cause circling behavior with increase in average speed. In one
embodiment, the animal was optogenetically stimulated with 5 ms
pulses at 20 Hz. Stimulation can be wirelessly controlled in
discrete (e.g., 20-second) on-off cycles. Representative traces of
mouse movement during on-off cycles are shown. In one example, the
circling rate of mice increases from 0.46 turns/minute to 2.4
turns/minute, (n=5 ChR2+ mice, P=0.0148, effect size=0.633), as
shown in FIGS. 5d-f. The mean speed of mice, normalized by each
mouse's maximum speed, increased by 40% compared to no optogenetic
stimulation, and this behavior was replicated for multiple test
subjects. The cohort mean shown in FIG. 5f was tested to be (n=5
ChR2 mice, P=0.0025, effect size=2.4).
The implantable devices of the present disclosure can also be used
to stimulate nerve cuffs and optical fibers to control spinal cord
and peripheral nerve circuits in animals such as rodents. The small
size of the wireless implants described herein allows for easy
targeting of neural structures outside of the brain, such as the
spinal cord, without affecting locomotion. The wireless implantable
devices described herein can be configured to stimulate
ChR2-expressing, unmyelinated nociceptors at the spinal cord in
freely moving animals. FIG. 6a shows the device of FIG. 2b
implanted on the right side of the dorsal surface of a vertebra in
a mouse. A small hole can be drilled through the vertebra to
provide a window for light delivery to the spinal cord (e.g., to
L3/L4 of the spinal cord). FIG. 6b is a chart showing stimulation
of the spinal cord (10 Hz frequency, 10 ms pulse width, 10 mW/mm2
light power density). ChR2+ mice show increased unilateral c-Fos
expression during light stimulation compared to YFP+ mice (n=6
ChR2+ mice, 7 YFP+ mice, P=0.02, effect size=1.5).
The implantable devices of the present disclosure can also be used
to stimulate peripheral nerve endings. FIG. 7a shows the device of
FIG. 2c implanted subcutaneously adjacent to the triceps surae
muscles of a mouse with the micro-LED of the device routed to the
heel. FIG. 7b shows quantification of c-Fos expression that
confirms unilateral activation of ChR2 after optogenetic
stimulation (e.g., 10 minute stimulation at 10 ms, 10 Hz, 10
mW/mm2). Unilateral c-Fos expression is significantly greater in
ChR2+ mice compared to YFP controls (n=3 ChR2+ mice, n=2 YFP+ mice,
P=0.04, effect size 2.22).
To demonstrate the utility of the wirelessly powered implants in
studying operant behavior, mice were allowed to freely explore a
two-chamber place aversion setup in which one floor was resting
directly above the resonant cavity, as shown by FIG. 7c. After a
10-minute power-off habituation to the environment, mouse location
within the two chambers was measured for 10 minutes followed by 15
minutes with the implant wirelessly powered on. The ChR2-expressing
mice spent significantly less time in the resonant cavity chamber
than the non-resonant cavity chamber compared to control
YFP-expressing mice, as illustrated in FIGS. 7d-f. (n=5 ChR2 mice,
6 YFP mice, P=0.039, effect size=1.33).
The a miniature, light-emitting implants described herein can
safely and effectively stimulate neurons in the brain, spinal cord,
and peripheral nervous system with a micro-LED. This optogenetic
system permits untethered animal movement in a diverse array of
behavioral testing environments and has greatly reduced mass and
volume in order to minimize interference with natural animal
behavior.
Care should be taken when modifying this device with less efficient
LEDs or when driving the blue LED with higher powers than reported
here; increased power will increase both general heating of the
animal by the RF field as well as local tissue heating at the LED,
potentially beyond acceptable thermal thresholds. Also, it is
important to consider how light power varies as a function of
device orientation and position above the resonant cavity. A
smaller enclosure can also reduce the power variability, although
the reported system was sufficient to elicit reliable optogenetic
control of behavior. Circuitry designed to regulate the output
power in future iterations of this technology could provide more
constant power.
In some embodiments, the implantable devices described herein can
include sensing features and closed-loop control, as well as
multiple light colors to match the vast array of available
spectrum-sensitive opsins. Many other targets, including deeper
regions of the brain, other peripheral nerves, nerve plexuses, and
ganglia can also be targeted with this wireless technology. The
resonant cavities can also be further designed to decrease
variability in field strength, to allow for animal behavior in
different shaped enclosures, to account for animal behavior tests
in water, which has different dielectric properties than air, and
to allow for optogenetic stimulation in larger mammals.
The small size and mass of this optogenetic system may enable the
development of new optogenetics experiments with very little
modification of the core technology, including chronic optogenetic
stimulation of mice in their home-cage, stimulation while
navigating constricting obstacles, simultaneous stimulation of
multiple, socializing animals, simultaneous stimulation of multiple
neural targets in the same animal, and stimulation of deep neural
targets outside of the brain, for example, branches of the vagus
nerve or components of the enteric nervous system. This optogenetic
system simplifies light delivery and paves the way for more natural
behavior during optogenetic experiments.
Wireless power transfer enables electronics to be continuously
powered within a defined electromagnetic region. Techniques for
power transfer through biological tissue are generally based on
inductive coupling, which relies on the exchange of energy between
an implanted coil and an external coil through a quasi-static
magnetic field. The efficiency of power transfer can be
substantially enhanced by operating the coils at simultaneous
resonance, but the efficiency remains limited for coils with highly
asymmetric sizes. As a result, wireless systems demonstrated prior
to the present invention have required large power harvesting
stages that are mounted on the head of an animal subject. Even
then, tissue heating due to exposure to electromagnetic fields
remains an important problem.
To allow natural behavior, particularly with multiple subjects,
efficient power transfer to fully-implanted electronic devices is
required. In this disclosure, an alternative approach is disclosed
in which energy is extracted from a cavity resonator by the animal
subject. Power can be transferred to highly miniaturized electronic
devices within a region sufficiently large to allow freely moving
behavior. Due to the low power requirements for most electronic
functions, power sufficient for most experimental tasks can be
delivered under safe exposure levels.
FIG. 8 shows a power transmitter 101 comprising cylindrical
resonant cavity 104 in air with one of the flat surfaces replaced
by a conductive mesh or surface lattice 106 of subwavelength
apertures. The resonant cavity can further include a plurality of
monopole feeds 107. Due to the subwavelength dimensions of the
apertures, radiative energy transported out of the resonant cavity
is minimal, while an evanescent field is formed at the surface of
the mesh. At microwave frequencies, dispersion results in high
dielectric permittivity values for nearly all types of biological
tissue. As well-defined dielectric volumes, small animals support
distinct electromagnetic modes. When the subject is brought in
close proximity to the surface lattice, modes are coupled through
the evanescent field, allowing energy to tunnel from the resonant
cavity into the subject.
The energy extraction process is described by the coupled-mode
equations: {dot over
(.alpha.)}.sub.1(t)=(-i.omega..sub.1-.gamma..sub.1).alpha..sub.-
1+.kappa..alpha..sub.2+F (1) {dot over
(.alpha.)}.sub.2(t)=(-i.omega..sub.2-.gamma..sub.2).alpha..sub.2+.kappa..-
alpha..sub.1 (2)
where .alpha..sub.1 and .alpha..sub.2 are the mode amplitudes,
defined such that the energy in the objects are given by
|.alpha..sub.1|.sup.2 and |.alpha..sub.2|.sup.2. Here,
.omega..sub.1 and .omega..sub.2 are the resonant frequencies of the
resonant cavities, .kappa. the coupling coefficient, and F the
driving force provided to the initial resonant cavity. In absence
of the tissue volume, the steady-state amplitude has a time
dependency of exp(-i.omega..sub.1t-.gamma..sub.1).
To examine the coupling between the source resonator and the
tissue, .kappa. is solved for by describing the fields in the
source and the tissue by their normalized field patterns e.sub.1
and e.sub.2 respectively, assuming that the total field in the
system is given by the superposition:
E=.alpha..sub.1(t)e.sub.1+.alpha..sub.2(t)e.sub.2. (3)
Normalization is achieved by finding the field value over the
summed field intensities over the space:
.intg..times..times. ##EQU00001##
The rate of change of the energy in the tissue as a result of
coupling can be written as:
.times..gamma..times..kappa..times..times..times..kappa..times..times.
##EQU00002##
The evanescent field outside the source resonant cavity induces a
polarization current in the tissue given by:
j.omega.P.sub.21=j.omega.(.di-elect cons..sub.2-.di-elect
cons..sub.0).alpha..sub.1e.sub.1 (6)
where the term .di-elect cons..sub.2-.di-elect cons..sub.0 accounts
for the polarization current j.omega..di-elect cons..sub.0P.sub.21
in air.
Over the tissue volume, the transferred energy is given by the
equation:
.times..times..times..intg..times..times..times..omega..times..times..tim-
es..times..times..times..times..intg..times..times..times..omega..function-
. .times..times..times..times..times. ##EQU00003##
A comparison of (4) and (7) yields the coupling coefficient:
.kappa..times..omega..times..intg..times.
.times..times..times..times..intg..times. .times..times..times.
##EQU00004##
The power transfer efficiency to the tissue is given by:
.eta..gamma..times..gamma..times..gamma..times..times..kappa..times..time-
s..times..times. ##EQU00005##
The space of suitable dimensions for a cylindrical cavity
resonator, supporting only the lowest order (TM.sub.110) mode, was
established by the following equation:
.omega..mu..times. .times..times..times..pi. ##EQU00006##
where n, m, and l represent the number of half-period variations
along the x, y, and z directions. The p.sub.nm are the
corresponding roots described by a set of eigenvalues corresponding
to the TM.sub.nm modes of a cylindrical waveguide. Given the set of
possible heights, h, and radii, r, one specific embodiment
comprises a h=14.5 cm and r=10.5 cm. The top of the metallic
resonant cavity can be a high-density hexagonal mesh. Because the
dimensions of the unit cell are subwavelength, radiation from the
top is minimal, although the quality factor Q noticeably decreases
with increasing grid size. As such, the aperture dimensions of the
hexagonal grid can be chosen to optimize the resonator quality
factor and coupling to the animal subject.
The resonant cavity can be excited by two or more orthogonal
monopole feeds with a .pi./2 phase difference. The phase shift
generates a circularly polarized (CP) mode such that the power
transfer is invariant to the transverse orientation of the device.
The resonant cavity and implantable devices described herein enable
wireless powering of fully-implanted devices. This power transfer
exhibits high uniformity across a surface and results in minimal
radiative exposure for the experimenter. The described systems have
considerable potential for investigating the neural basis for
behaviors involving multiple interacting subjects.
As for additional details pertinent to the present invention,
materials and manufacturing techniques may be employed as within
the level of those with skill in the relevant art. The same may
hold true with respect to method-based aspects of the invention in
terms of additional acts commonly or logically employed. Also, it
is contemplated that any optional feature of the inventive
variations described may be set forth and claimed independently, or
in combination with any one or more of the features described
herein. Likewise, reference to a singular item, includes the
possibility that there are plural of the same items present. More
specifically, as used herein and in the appended claims, the
singular forms "a," "and," "said," and "the" include plural
referents unless the context clearly dictates otherwise. It is
further noted that the claims may be drafted to exclude any
optional element. As such, this statement is intended to serve as
antecedent basis for use of such exclusive terminology as "solely,"
"only" and the like in connection with the recitation of claim
elements, or use of a "negative" limitation. Unless defined
otherwise herein, all technical and scientific terms used herein
have the same meaning as commonly understood by one of ordinary
skill in the art to which this invention belongs. The breadth of
the present invention is not to be limited by the subject
specification, but rather only by the plain meaning of the claim
terms employed.
* * * * *
References